Chlamydocin is a highly cytostatic cyclic tetrapeptide produced by cultures of Diheterospora Chlamydosporia. AT 0.3 x 10 to the -9 g/ml, it inhibits the growth of P-815 mouse mastocytoma cells in vitro more efficiently than actinomycin D, amethopterin, colchicine or vincristine. Chlamydocin has low mammalian toxicity because it is rapidly inactivated in vivo in the blood. For this reason, the onconstatic activity by injection is low; although when administered by interarterial perfusion, the onconstatic activity is substantial. Preliminary mechanism of action studies carried out here suggests that chlamydocin inhibits a process which is essential to the induction of the synthesis of new proteins rather than the process of protein synthesis itself. The objective of this research is to synthesize chlamydocin, study its mechanism of inactivation and prepare new analogs with improved half-lives and specificities. Using radioactive chlamydocin, the site of alkylation will be determined and attempts will be made to identify chlamydocins receptor in PHA/TPA activated lymphocytes. Systematic studies of the relationships between peptide ring-system conformation and biological activity in vitro and in vivo will be carried out. Additional work to correlate activity of HC-toxin, a host-specific phytotoxin we have shown also is a potent inhibitor in our assay system, with structure is planned. These studies are directed toward an understanding of the medicinal chemistry and site of action of this novel biologically active peptide.